Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, People's Republic of China.
Int J Nanomedicine. 2020 Dec 17;15:10271-10284. doi: 10.2147/IJN.S275846. eCollection 2020.
Cancer theragnosis involving cancer diagnosis and targeted therapy simultaneously in one integrated system would be a promising solution of cancer treatment. Herein, a convenient and practical cancer theragnosis agent was constructed by combining gold nanocages (AuNCs) covered with selenium and a chitosan (CS) shell (AuNCs/Se) to incorporate the anti-cancer drug doxorubicin (DOX) as a multifunctional targeting nanocomposite (AuNCs/DOX@Se-iRGD) for photoacoustic imaging (PAI)-guided chemo-photothermal synergistic therapy that contributes to enhanced anti-cancer efficacy. The novel design of AuNCs/DOX@Se-iRGD gives the nanocomposite two outstanding properties: (1) AuNCs, with excellent LSPR property in the NIR region, act as a contrast agent for enhanced PAI and photothermal therapy (PTT); (2) Se acts as an anti-cancer nanoagent and drug delivery cargo.
The photothermal performance of these nanocomposites was evaluated in different concentrations with laser powder densities. These nanocomposites were also incubated in pH 5.3, 6.5, 7.4 PBS and NIR laser to study their drug release ability. The cellular uptake was studied by measuring the Se and Au concentrations inside the cells using inductively coupled plasma-mass spectrometry (ICP-MS). Besides, in vitro and in vivo anti-tumor activity were carried out by cytotoxicity assay MTT and tumor model nude mice, respectively. As for imaging, the PA value and images of these nanocomposites accumulated in the tumor site were sequentially collected at specific time points for 48 h.
The prepared AuNCs/DOX@Se-iRGD showed excellent biocompatibility and physiological stability in different media. In vivo results indicated that the targeting nanocomposite presented the strongest contrast-enhanced PAI signals, which could provide contour and location information of tumor, 24 h after intravenous injection. Likewise, the combined treatment of chemo- and photothermal synergistic therapy significantly inhibited tumor growth when compared with the two treatments carried out separately and showed negligible acute toxicity to the major organs.
This study demonstrates that AuNCs/DOX@Se-iRGD has great prospect to become a multifunctional anti-tumor nanosystem for PAI-guided chemo- and photothermal synergistic therapy.
将癌症诊断和靶向治疗同时集成在一个系统中的癌症治疗方法将是癌症治疗的一个有前途的解决方案。在此，通过将硒和壳聚糖（CS）壳包裹的金纳米笼（AuNCs）结合起来，构建了一种方便实用的癌症治疗试剂，以将抗癌药物阿霉素（DOX）作为多功能靶向纳米复合材料（AuNCs/DOX@Se-iRGD）来进行光声成像（PAI）引导的化学-光热协同治疗，从而提高抗癌效果。AuNCs/DOX@Se-iRGD 的新颖设计使该纳米复合材料具有两个突出的特性：（1）AuNCs 在近红外区域具有优异的 LSPR 特性，可作为增强 PAI 和光热治疗（PTT）的造影剂；（2）Se 作为抗癌纳米药物和药物输送载体。
通过改变激光粉密度评估了这些纳米复合材料在不同浓度下的光热性能。还在 pH 值为 5.3、6.5、7.4 PBS 和近红外激光中孵育这些纳米复合材料，以研究其药物释放能力。通过电感耦合等离子体质谱法（ICP-MS）测量细胞内的硒和金浓度来研究细胞摄取。此外，通过 MTT 细胞毒性测定和肿瘤模型裸鼠分别进行了体外和体内抗肿瘤活性实验。至于成像，在 48 小时内，依次在特定时间点收集这些纳米复合材料在肿瘤部位的 PA 值和图像。
所制备的 AuNCs/DOX@Se-iRGD 在不同介质中表现出良好的生物相容性和生理稳定性。体内结果表明，靶向纳米复合材料在静脉注射后 24 小时内表现出最强的对比增强 PAI 信号，可提供肿瘤的轮廓和位置信息。同样，与单独进行的两种治疗相比，化学-光热协同治疗的联合治疗显著抑制了肿瘤生长，并且对主要器官没有明显的急性毒性。
本研究表明，AuNCs/DOX@Se-iRGD 有望成为一种用于 PAI 引导的化学-光热协同治疗的多功能抗肿瘤纳米系统。
